EP4202434A1 - System zur elektrosprayionisierung mit integrierter lc-säule und elektrospray-emitter - Google Patents

System zur elektrosprayionisierung mit integrierter lc-säule und elektrospray-emitter Download PDF

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Publication number
EP4202434A1
EP4202434A1 EP22212989.2A EP22212989A EP4202434A1 EP 4202434 A1 EP4202434 A1 EP 4202434A1 EP 22212989 A EP22212989 A EP 22212989A EP 4202434 A1 EP4202434 A1 EP 4202434A1
Authority
EP
European Patent Office
Prior art keywords
emitter
electrically conductive
column
protective sleeve
enabled
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP22212989.2A
Other languages
English (en)
French (fr)
Inventor
Brandon Howard Robson
Xuefei Sun
Carla Marie Medlin
Shane Bechler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dionex Corp
Original Assignee
Dionex Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dionex Corp filed Critical Dionex Corp
Publication of EP4202434A1 publication Critical patent/EP4202434A1/de
Pending legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
    • G01N30/724—Nebulising, aerosol formation or ionisation
    • G01N30/7266—Nebulising, aerosol formation or ionisation by electric field, e.g. electrospray
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6004—Construction of the column end pieces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/60—Construction of the column
    • G01N30/6047—Construction of the column with supporting means; Holders
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/64—Electrical detectors
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H01J49/0431—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components for liquid samples
    • H01J49/0445—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components for liquid samples with means for introducing as a spray, a jet or an aerosol
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • H01J49/167—Capillaries and nozzles specially adapted therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N2030/022—Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027—Liquid chromatography

Definitions

  • the present disclosure generally relates to the field of liquid chromatography including a system for electrospray ionization with integrated liquid chromatography (LC) column and electrospray emitter.
  • LC liquid chromatography
  • proteomics being the study of protein structure and function, is a research focus for decades to come as it can allow one to elucidate the fundamentals of life and the molecular basis of health and disease. Analysis of complex protein mixtures usually involves two steps: molecular separation and identification/characterization.
  • proteins are subject to proteolytic digestion to break down into fragments of peptides which are then separated, usually with liquid chromatography (LC), before being introduced into an ion source of a mass spectrometer.
  • LC liquid chromatography
  • the ion source for proteomics experiments implements electrospray ionization (ESI) to ionize the peptide to form ions that can be transported among components of a mass spectrometer.
  • ESI electrospray ionization
  • the commonly used interface between chromatography and mass spectrometry is made up by the electrospray ion-source.
  • the eluate from the LC column is passed through an emitter (also termed a needle) that is held at an electric potential that usually differs by one or more kilovolts from an opposing inlet orifice of the mass spectrometer.
  • an emitter also termed a needle
  • the physical characteristics of a LC column and an ESI emitter affect analytical performance.
  • stationary phase chemistry For example, stationary phase chemistry, stationary phase particle size, diameter, length, and post-column dead volume of the LC column influence separation efficiency of chromatography.
  • solution resistances cause a voltage drop that reduces the magnitude of the voltage applied to the tip of the emitter, affecting the formation of ions.
  • the high electric potential differences present a safety hazard if the charged areas can be touched by the operator.
  • the electrospray emitter is a thin fragile component that is potentially easy to damage if not handled carefully and moreover is sharp such that injury can be caused by it. It is therefore desirable to reduce the risk of damage to the electrospray emitter and/or injury by exposure to it.
  • an integrated system for liquid separation and electrospray ionization can include an emitter-enabled capillary column including an emitter portion and a column portion and a retractable protective sleeve for covering and/or supporting the emitter portion along at least a portion of its axis.
  • the protective sleeve can be slidably mounted around the emitter-enabled capillary column.
  • the retractable protective sleeve can be moveable to an extended position wherein a tip of the emitter portion is covered by the protective sleeve.
  • a resilient member can be provided to bias the protective sleeve towards the extended position wherein it covers the tip of the emitter portion.
  • the protective sleeve can be enclosed and moveable within an outer electrically conductive sheath adapted for insertion within a holder having a high-voltage contact point.
  • the electrically conductive sheath can be adapted to contact the high-voltage contact point and provide an electrical connection to enable the emitter-enabled capillary column to receive a high voltage.
  • the electrically conductive sheath can have a recess to receive the high-voltage contact point.
  • the retractable protective sleeve can be moveable to a retracted position wherein a tip of the emitter-enabled capillary column is uncovered.
  • the emitter-enabled capillary column can be embedded in a plastic material.
  • the stationary phase can be held in place by a porous matrix in the emitter tip.
  • the emitter-enabled capillary column can be a liquid chromatography (LC) column.
  • LC liquid chromatography
  • the emitter-enabled capillary column can be coiled in a loop.
  • the electrospray emitter can include a fused silica capillary, a metal capillary, a ceramic capillary, or a glass capillary.
  • the high-voltage contact point can include an electrically conductive ball.
  • the electrically conductive ball can fit in the recess in the outer surface of the electrically conductive sheath, and wherein the recess is a groove.
  • the electrically conductive sheath can be electrically connected to an electrically conductive body.
  • the electrically conductive body can be connected to an electrically conductive cap or union wherein the electrically conductive cap or union can be in direct contact with the eluent moving through the emitter-enabled capillary column.
  • the holder is fixed on a mass spectrometer.
  • Embodiments of a system for electrospray ionization with integrated liquid chromatography (LC) column and electrospray emitter are described herein.
  • a “system” sets forth a set of components, real or abstract, comprising a whole where each component interacts with or is related to at least one other component within the whole.
  • One technique to improve the analytical performance of the LC column and the ESI emitter is to combine the functionality of the emitter with the LC column into a single component, also referred to as a "packed-tip" design or an emitter-enabled capillary column. That is, the LC column can include an end that is pulled to a tip to implement the emitter, resulting in a single structure forming the LC column and the emitter. Due to the integration of the emitter with the LC column in a single structure, the post-column dead volume (i.e., the volume after the LC column and before a detector) is reduced, thereby reducing post-column peak broadening. This results in an increase, or ideal state, in the chromatographic performance.
  • the post-column dead volume i.e., the volume after the LC column and before a detector
  • the Easy Spray column format includes a retractable protective sleeve around the emitter tip, a temperature control PCB board, and an inlet frit on the capillary column to prevent the loss of media from the column
  • Fig. 1A shows an external view of an integrated system 100
  • Fig. 2A shows a cross section view of the integrated system 100
  • Fig. 3A shows an exploded view of the integrated system 100.
  • Integrated system 100 comprising an emitter-enabled capillary column 102 with a distal end 104 pulled to a tip to function as an electrospray emitter.
  • the emitter-enabled capillary column 102 includes a column portion and an emitter portion.
  • the column portion is an LC column, e.g. HPLC column.
  • the LC column may be used with various flow rates, e.g. down to as low as nano-LC flow rates, i.e. 100 nL/min or less.
  • the column portion of the emitter-enabled capillary column 102 is coiled into a loop 106 comprising multiple column windings to increase the separation length. This enables space saving since it allows a column to take up less space than if it were laid straight and it permits different column lengths to be used in the same design of integrated system, i.e. by changing the number of windings in the coil. Coiling the column further makes the column compact and able to fit into a small volume that may more easily be temperature controlled by a heating element than if it were laid straight and would occupy an elongated, typically long, space.
  • the emitter portion includes an electrospray emitter.
  • the electrospray emitter can include an electrically conductive capillary, such as a metal capillary or a glass capillary, e.g. glass coated with electrically conductive material. However, glass capillaries that are not conductive or coated may be used.
  • the distal end 104 with integrated emitter tip can include a porous matrix.
  • the porous matrix can reduce the void volume of the tip. Additionally, the porous matrix can provide a defined end to the column portion to ensure consistent packing of column material.
  • the emitter-enabled capillary column 102 is embedded in a molding part 108.
  • the molding part 108 comprises a plastic material, for example, a thermoplastic material, for example, polyamide and polyurethane based MacroMelt TM . Suitable methods to embed the assembly are described in the applicant's patent US Pat 9302415 .
  • a proximal end 110 of the emitter-enabled capillary column 102 is provided with fitting 112, e.g. for connection to an injector or other HPLC components.
  • the fitting 112 can include a ferrule 114, a nut 116, and cap 118.
  • the fitting 112 can include a plug type end fitting 202 with cap screw 204 and an external union with small internal diameter 206, as shown in Figs. 1B , 2B , and 3B .
  • the plug type end fitting 202 can include a conductive sleeve 208 and non-conductive sleeve 210.
  • one or more sleeves 120 and 122 can be provided to protect the emitter-enabled capillary column 102 and form a seal with other HPLC components at the fitting 112.
  • the molding 108 provides rigidity to the system, as well as provides a shield against a user disassembling or damaging, intentionally or by accident, the fittings, HPLC column and emitter.
  • a protective sleeve 124 of generally cylindrical form is slidably located on the distal end 104 of the emitter-enabled capillary column 102.
  • the sleeve has a main body 126 and a base 128 of wider diameter than the main body.
  • the protective sleeve 124 is desirably made of a rigid material, such as a metal or polymer material. In this way the rigidity of the sleeve can protect the fragile emitter portion of the emitter-enabled capillary column 102 that it covers.
  • Mounted about the protective sleeve 124 is an electrically conductive sheath 130, e.g. made of metal.
  • the conductive sheath 130 has an internal diameter such as to accommodate therein the protective sleeve 124 and permit the protective sleeve 124 to slidably move in a reciprocating manner inside the sheath as further described below.
  • the electrically conductive sheath 130 is supported at one end by a supporting structure 132.
  • the supporting structure includes a conductive nut 134, a metal body 136, and an additional nut 138.
  • the emitter-enabled capillary column 102 can be threaded through a sleeve 140, such as a PEEK sleeve, and the sleeve 140 and the emitter-enabled capillary column 102 can be held in place relative to the supporting structure 132 with ferrules 142 and 144.
  • the protective sleeve is fixed with respect to the emitter.
  • the protective sleeve is most preferably retractable, i.e. with respect to the emitter tip of the emitter-enabled capillary column 102. Where the sleeve is retractable, this ensures that the emitter tip is exposed when in use and thereby the sleeve does not interfere, for example, with gas flows and equipotential lines around the emitter tip.
  • a retractable sleeve when in use, does not block visibility of the emitter tip so one can readily monitor the spray.
  • the protective sleeve is preferably slidably located on the emitter-enabled capillary column 102.
  • the protective sleeve is preferably movable between an extended (or cover) position wherein it covers the emitter tip, and a retracted position wherein the emitter tip is exposed. When the emitter tip is exposed, it may be used for electrospray ionization.
  • the emitter tip herein means the tip from which ions are produced when in use.
  • the protective sleeve thus covers and supports the emitter-enabled capillary column 102 along at least a portion of its axis which includes the emitter tip.
  • a spring 146 is further provided inside the electrically conductive sheath 130, positioned in a space between the supporting structure 132 and the protective sleeve 124.
  • the spring 146 acts upon the base of the protective sleeve to bias the protective sleeve 124 to force it out of the electrically conductive sheath 130.
  • the length of the sleeve 124 and its extension out of the sheath is sufficient to cover the tip of the emitter-enabled capillary column 102 and act to protect it against damage.
  • a part of the main body 126 of the protective sleeve 124 protrudes outside the sheath 130 and thereby covers the emitter.
  • the extent of travel of the sleeve 124 out of the sheath 130 is restricted by a reduced internal diameter at the end of the sheath 130 that stops the wider diameter base 128 of the sleeve. If a force is applied to the sleeve 124 to push the sleeve backwards into the sheath 130, the spring 146 becomes compressed and the tip of the emitter becomes exposed and ready for use.
  • the spring is provided in contact with the protective sleeve to bias the sleeve towards its extended position.
  • the spring is preferably in contact with the base of the protective sleeve. In this way, the spring, upon activation, is able to force the sleeve to cover the emitter tip when it is required to be protected.
  • the spring also allows the sleeve to be retracted from the emitter tip when the integrated system is assembled with an instrument for mass spectrometric analysis. To enable this retraction, preferably the spring is forced into a compressed state, e.g. by pushing the sleeve towards the spring.
  • the spring biases the sleeve to the extended position such that the sleeve adopts the extended or cover position when the sleeve does not have a sufficient force applied pushing it against the spring.
  • the spring thereby enables the protective sleeve to cover the tip end of the emitter when the emitter is not required to be used such as when the integrated system is disassembled from an instrument for mass spectrometric analysis.
  • the protective sleeve is preferably enclosed within the electrically conductive sheath.
  • the electrically conductive sheath 130 is preferably fixed in position in relation to the emitter-enabled capillary column 102.
  • the protective sleeve is preferably capable of reciprocating motion within the electrically conductive sheath 130, thereby enabling the protective sleeve to be retractable with respect to the emitter-enabled capillary column 102.
  • the spring is also preferably provided inside the electrically conductive sheath 130 for providing a force against the sleeve, more preferably against the base of the sleeve, to bias the sleeve towards the extended position.
  • the spring is provided inside the electrically conductive sheath, whereby the spring, upon activation, is able to force the sleeve out of the electrically conductive sheath to cover the emitter.
  • the protective sleeve may be forced out as soon as the system is pulled out of a recipient holder, that is, the spring force is constantly acting so as to push the sleeve in an outwards direction thereby to cover the emitter tip.
  • the electrically conductive sheath 130 can be enclosed within a holder having a high-voltage contact point when the integrated system is in use.
  • the holder can be a holder located on an instrument, e.g. for mass spectrometric analysis.
  • the electrically conductive sheath 130 provides an electrical connection to enable the emitter to receive a high voltage.
  • the sheath may provide an electrical connection to the emitter-enabled capillary column 102 either directly or via one or more intermediate electrically conductive bodies, e.g. the protective sleeve or the fitting.
  • the electrically conductive sheath 130 has a recess in the form of a circumferential groove 148 in its outer surface for making an electrical contact with a high voltage contact, e.g. a contact ball.
  • the electrical path can include the electrically conductive sheath 130, the conductive nut 134, the metal body 136, a conductive wire 150, and cap 118 or union 206.
  • the nut 116 and additional nut 138 can be non-conductive and not included in the electrical path.
  • one or more of nuts 116 and 138 can be electrically conductive and form part of the electrical path.
  • the cap screw 204 can be non-conductive and not included in the electrical path.
  • cap screw 204 can be electrically conductive and form part of the electrical path.
  • the electrically conductive sheath 130 is electrically connected to the fitting 112 that connects the emitter-enabled capillary column 102 to the upstream components and the fitting 112 electrically contacts the electrically conductive liquid (eluent) at the point of entering the emitter-enabled capillary column 102, thereby enabling the transfer of charge from the high voltage contact point to the tip of the emitter.
  • the plastic molding 108 covers the integrated system with the electrically conductive sheath 118 mounted at the front end and the protruding sleeve 124 protecting the emitter distal end 104 of the emitter-enabled capillary column 102. It will be appreciated from the description that the whole integrated system is thus formed as a type of cartridge for use with an instrument, e.g. mass spectrometer. An emitter cap 152 can cover the electrically conductive sheath when not in use.
  • the integrated separation column may be equipped with one or more embedded components of: a heating and/or cooling element and a thermal sensor in close proximity or contact with the column and preferably embedded in the plastic material.
  • channels for gas flow may also be embedded in the plastic material; the outlet of these channels being in close proximity with the apex (tip) of the emitter, whereby gas leaving the outlet assists in the desolvation of the spray cloud.
  • the embedded components may further comprise an identification tag, such as a radio frequency identification tag (RFID) embedded in the plastic material.
  • RFID radio frequency identification tag
  • plastifying the plastic material that is used for embedding the integrated system may be achieved in various ways, preferably by heating the plastic material beyond the softening temperature for bringing it in its softening range and making it soft.
  • the entire column and fittings are surrounded by the plastic material.
  • the plastic material may be provided as a plastic molding part.
  • the molding part may be a pre-formed part adapted to the shape of the integrated separation column and of the forming tool.
  • the forming of the molding part may be achieved by closing the forming tool and exerting pressure on the pre-formed part. Alternatively, this is achieved by closing the forming tool and heating the forming tool together with the plastic material.
  • the forming of the molded part may be achieved by injecting molten plastic material into a mold wherein the LC column with fittings and other related or required components are located and allowing the molten plastic to embed these parts and cool off and harden to become solid.
  • the molded part may be shaped by exerting pressure on the plastic material caused by the thermal expansion of the plastic material by heating the closed forming tool comprising the plastic material, alternatively by exerting pressure on the plastic material by closing the forming tool, or actively cooling down the plastic material and/or the forming tool.
  • Still another alternative embodiment may be achieved by mixing chemicals that subsequently polymerize inside a mold thereby embedding the LC column with fittings and other related components such as the emitter.
  • the plastic material used in the method of the present invention may be thermoplastic material or thermosetting material.
  • the plastic material is at least one of: a thermoplastic material, polyetheretherketone (PEEK), one of a broad range of fluoropolymers, in particular perfluoroamines (PFA) or fluorinated ethylene-propylene copolymer (FEP), duroplastic material or compound, in particular polyimide, and liquid crystal polymers (LCP).
  • PEEK polyetheretherketone
  • FEP fluorinated ethylene-propylene copolymer
  • LCP liquid crystal polymers
  • the plastic materials of the present invention are thermoplastic hotmelts based on polyamide, such as those marketed under the tradename MacroMelt (Henkel Mathanditgesellschaft). These includes at least one room-temperature-flowable polymerizable compound in combination with a polymeric matrix present in an amount sufficient to render the composition non-flowable at temperatures of at least about 49° C.
  • the polymerizable compound or composition may be selected from a wide group of materials including anaerobics, epoxies, acrylics, polyurethanes, olefinic compounds and combinations thereof. Anaerobic compositions are most desirable since they have unique applications in many threadlocking and sealant areas where the need for a non-flowable material exists.
  • the polymeric matrix may be selected from polyamides, polyacrylamides, polyimides, polyhydroxyalkylacrylates and combinations thereof.
  • an anaerobic adhesive composition which includes a polymerizable (meth) acrylate monomer, a polymerization initiator for the monomer, and a polymeric matrix material miscible or otherwise compatible with the monomer.
  • the matrix material is present in an amount sufficient to render the composition non-flowable at temperatures of at least about 210° C.
  • the polymeric matrix and polymerizable component readily form a stable mixture or combination without phase separation of component parts.
  • preferred embodiments of the present invention are also directed to an integrated separation column comprising end fittings embedded in a plastic material, irrespective of the method used for the embedment in the plastic material.
  • the integrated separation column may further comprise an electrospray emitter directly connected with the separation column through one of the end fittings.
  • the plastic material is at least one of: a thermoplastic material, preferably based on polyamide and/or polyurethane, polyetheretherketone (PEEK), one of a broad range of fluoropolymers, in particular perfluoroamines (PFA) or fluorinated ethylene-propylene copolymer (FEP), duroplastic material or compound, in particular polyimide, liquid crystal polymers (LCP).
  • a thermoplastic material preferably based on polyamide and/or polyurethane, polyetheretherketone (PEEK), one of a broad range of fluoropolymers, in particular perfluoroamines (PFA) or fluorinated ethylene-propylene copolymer (FEP), duroplastic material or compound, in particular polyimide, liquid crystal polymers (LCP).
  • the integrated separation column may in agreement with the other described embodiments of the present invention further comprise one or more of: an RFID-tag, heating/cooling elements and thermo sensor, a high-voltage contact point for the electrospray emitter, counter electrode(s) with a geometry that benefits definition of the field lines around the electrospray emitter, and channels for gas flow embedded in the plastic material.
  • Coupling with a laboratory apparatus becomes easier. Additionally, an exact and repeatable positioning process of the integrated column relatively to the frame can be guaranteed by molding the plastic material to a shape that provides a close or tight fit in a receiving holder on the laboratory apparatus. The ease and accuracy of the positioning may be further enhanced by use of shapes that by design help lock the two items into a given position (e.g. by way of convex/concave mating surfaces, magnets or spring loads). This also enables the exact positioning of the integrated column into a laboratory apparatus if the holder is positioned precisely in the laboratory apparatus.
  • Nano-LC columns are frequently and advantageously made from a piece of silica glass tubing where said tubing typically is 10 mm to 1000 mm long but has an outer diameter of around 300 ⁇ m and hence the tubing can easily break.
  • silica glass tubing typically has an outer polymer lining of a few micrometers thickness that renders some strength but the glass tubing is still easily broken.
  • the emitter is made from a very narrow piece of metal or glass tubing and can readily be damaged by contact with other items.
  • the plastic embedding described herein makes the integrated column robust and durable such that they cannot readily break by accident.
  • the protection of the column and emitter includes protection from physical strains, twists, bends as well as the pressure of the liquid inside the tubing whose thin walls are made several fold thicker by the plastic matrix being in direct (chemical) contact with the outer surface of the tubing.
  • chromatographic retention times that are observed for the individual analytes are highly dependent on the temperature at which the separation takes place. Slight variation in temperature can lead to pronounced shifts in retention times and in order to obtain reproducible data, it is often sought to maintain stable ambient temperatures for the column. NanoLC columns-by virtue of their small diameters-can readily exchange heat with the surrounding air. This is however prevented by the plastic matrix which provides thermal insulation of the columns and therefore assists in maintaining stable column temperatures.
  • the specification may have presented a method and/or process as a particular sequence of steps.
  • the method or process should not be limited to the particular sequence of steps described.
  • other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims.
  • the claims directed to the method and/or process should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the various embodiments.
EP22212989.2A 2021-12-21 2022-12-13 System zur elektrosprayionisierung mit integrierter lc-säule und elektrospray-emitter Pending EP4202434A1 (de)

Applications Claiming Priority (1)

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US17/557,698 US20230194482A1 (en) 2021-12-21 2021-12-21 System for electrospray ionization with integrated lc column and electrospray emitter

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EP4202434A1 true EP4202434A1 (de) 2023-06-28

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EP (1) EP4202434A1 (de)
CN (2) CN116297894A (de)

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